APOE-ε4-related differences in left thalamic microstructure in cognitively healthy adults
Open accessAbstract
APOE-ε4 is a main genetic risk factor for developing late onset Alzheimer’s disease (LOAD) and is thought to interact adversely with other risk factors on the brain. However, evidence regarding the impact of APOE-ε4 on grey matter structure in asymptomatic individuals remains mixed. Much attention has been devoted to characterising APOE-ε4-related changes in the hippocampus, but LOAD pathology is known to spread through the whole of the Papez circuit including the limbic thalamus. Here, we tested the impact of APOE-ε4 and two other risk factors, a family history of dementia and obesity, on grey matter macro- and microstructure across the whole brain in 165 asymptomatic individuals (38–71 years). Microstructural properties of apparent neurite density and dispersion, free water, myelin and cell metabolism were assessed with Neurite Orientation Density and Dispersion (NODDI) and quantitative magnetization transfer (qMT) imaging.APOE-ε4 carriers relative to non-carriers had a lower macromolecular proton fraction (MPF) in the left thalamus. No risk effects were present for cortical thickness, subcortical volume, or NODDI indices. Reduced thalamic MPF may reflect inflammation-related tissue swelling and/or myelin loss in APOE-ε4. Future prospective studies should investigate the sensitivity and specificity of qMT-based MPF as a non-invasive biomarker for LOAD risk.
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More recent investigations have interrogated cortical or subcortical gray matter with inconclusive findings.
“more recent investigations have interrogated cortical or subcortical gray matter with inconclusive findings [9, 10].”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [9]
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References 130 · Cited by 15
- Authors
- Mole, J. P., Fasano, F., Evans, J., Sims, R., Kidd, E., Aggleton, J. P., & Metzler-Baddeley, C.
- Affiliations
- Cardiff University (GB)
- Siemens Healthineers (Germany) (DE)
- Venue
- Scientific Reports
- Published
- 2020-11-13
- Volume
- 10
- Issue
- 1
- Pages
- 19787-19787
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7666117
- OpenAlex
- W3098810472
- Cited by
- 15
- References
- 130
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 2
- FWCI
- 1.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
- Funders
- Wellcome Trust (103722/Z14/Z)
- Alzheimer's Society (208)
- BRACE (208)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- APOE ε4, thalamus, gray matter microstructure, late-onset Alzheimer's disease, macromolecular proton fraction, NODDI, quantitative magnetization transfer, family history of dementia, obesity, asymptomatic adults, demyelination, inflammation, Papez circuit, neuroimaging biomarkers
- MeSH terms
- Adult, Aged, Blood Pressure, C-Reactive Protein, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Prospective Studies, Risk Factors, Biomarkers, Interleukin-8, Apolipoprotein E4, White Matter, Gray Matter
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